1. Field of the Invention
The present invention relates to biologically active peptides having activities to inhibit Toxoplasma multiplication.
Toxoplasma gondii is a sort of protozoa, which can proliferate in almost all cells of various mammals and birds in all over the world to cause various apriori and aquired diseases, such as cerebromeningitis, for human being and also to cause severe diseases of domestic animals. Unlike other microorganisms, the Toxoplasma organism evades the killing action of macrophage even after being taken by the macrophage of a normal host to reveal repeated fissiparous multiplication due to endogeneous budding.
On the other hand, the effect of inhibiting multiplication of the parasites in macrophages or the protozoacidal function of macrophages has been observed in a toxoplasma-hyperimmune animal, and it has been known that the serum of such an animal contains a mediator (generally referred to as "lymphokine") for inhibiting multiplication of toxoplasma in the normal cells of the animal. (See Reference No. 1. References cited herein will be listed collectively in the last portion of the specification.)
It has also been known that a lymphokine which inhibits multiplication of Toxoplasma in the homologous cells is existing in the supernatant of the culture medium obtained by cultivating spleen cells derived from a toxoplasma-hyperimmune animal in the presence of Toxoplasma lysate antigen (TLA). (See Reference Nos. 2 and 3.)
The lymphokine is a glycoprotein having a molecular weight of from 30,000 to 40,000, which is estimated to be a T-lymphocyte producing substance and referred to as Toxo-GIF (Toxoplasma Growth Inhibitory Factor). (See Reference Nos. 2 and 3.) The Toxo-GIF inhibits multiplication of Toxoplasma not only in the macrophage but also in other somatic cells. However, it only inhibits multiplication or protozoa in the cells of the same animal species, and cannot inhibit multiplication of protozoa in the cells of different animal species. (See Reference Nos. 3 and 4.)
Due to the species specificity described above, the Toxo-GIF cannot be used for the prevention or curing of toxoplasmosis of human being or various animals other than the host.
Under these circumstances, we have previously found and proposed a novel and epoch-making low molecular weight polypeptide which inhibits multiplication of Toxoplasma and is prepared by hydrolysis of serum of a toxoplasma-immune animal. (See Reference Nos. 5, 6 and 7.) The hydrolysate of the serum originated from a toxoplasma-immune animal is general referred to as "Obioactin". (See Reference No. 8.) This Obioactin is a polypeptide having a molecular weight of from 3,000 to 5,000 and inhibits multiplication of Toxoplasma not only in the homologous cells but also in heterologous cells. (See Reference No. 9.) Furthermore, the Obioactin has anti-microbial activities against various microorganisms, other protozoa, bacteria and viruses and also has anti-tumor activity, and hence it is applicable in immunoactive compositions. (See Reference Nos. 5, 6, 7 and 17.)
However, since the Obioactin is a refined product of a portion of a toxoplasma-immune serum, it is demanded to clarify the structure thereof, particularly the active core or unit, and to enable basic analysis of the mechanism of its function and mass production thereof by synthetic process.